The purpose of this K01 is for the applicant, who is trained in behavioral research, to obtain additional training in brain imaging and genetics in relation to smoking and ADHD (Attention Deficit Hyperactivity Disorder). The short term goal is to obtain training in functional Magnetic Resonance Imaging (fMRI), neuroanatomy, drug abuse research, ethics, and genetics via: (1) formal coursework, (2) interactions with the primary mentor, Dr. James Swanson, and other accomplished researchers, and (3) an integrated research plan. The long term goal of such training is to provide the applicant with the skills to become an independent investigator on associations between smoking, brain activity, and genes using the R01 mechanism. The K01 research plan investigates the underlying mechanisms of smoking in 100 young adults from the Multimodal Treatment study of children with ADHD (MTA), which is a longitudinal clinical trial funded by the National Institutes of Health. All subjects in the MTA project have been clinically assessed and genetic data are available. The applicant will receive hands-on training in fMRI and genetics by examining the associations between smoking, prefrontal-limbic brain circuitry, dopamine genes, and ADHD. For this purpose, four groups of young adults will be recruited from the MTA study: (1) 25 smokers with ADHD;(2) 25 nonsmokers with ADHD;(3) 25 normative control smokers;and (4) 25 normative control nonsmokers. Smoking will be assessed via questionnaires and salivary cotinine levels. Prefrontal-limbic brain activity will be examined via fMRI. Candidate genes will be the dopamine receptor (DRD4) and transporter (DAT1). Each nonsmoker will undergo an fMRI scan during an experimental task consisting of mathematical problems and unpleasant and neutral pictures. Smokers will undergo two fMRI scans during similar experimental tasks under the following two conditions: (1) after smoking a cigarette and (2) after overnight abstinence. The findings will provide information on the effects of smoking and abstinence on prefrontal- limbic brain circuitry in smokers with and without ADHD. In addition, the study will explore the smoking in individuals with DRD4 and DAT1 and their potential interaction with prefrontal-limbic brain circuitry. Cigarette smoking is a major public health problem and individuals with ADHD are at an increased risk for smoking initiation and nicotine dependence. The short term goal of this K01 proposal is to provide a comprehensive training experience and to obtain a rich data set to understand the underlying mechanisms for smoking initiation and nicotine dependence in people with and without ADHD. In the long term, such research will aid in the development of evidence-based smoking cessation and prevention programs.